Regulation of porcine classical and nonclassical MHC class I expression

Abstract

Major histocompatibility complex (MHC) class I molecules comprise a family of polymorphic cell surface receptors consisting of classical 1 a molecules that present antigenic peptides and nonclassical 1 b molecules. Gene expression for human classical and nonclassical MHC class I molecules has been shown to be differentially regulated by interferon, with variation in the nucleotide sequence of promoter regions, resulting in differences in interferon inducibility and basal levels of gene transcription. In this study on porcine classical and nonclassical swine leukocyte Ag (SLA) class I molecules, we show alignments of putative regulatory elements in the promoters of the three functional classical class I genes, SLA-1, SLA-2, and SLA-3; two nonclassical 1 b genes, SLA-6 and SLA-7; and a MIC-2 gene. Promoter elements were cloned upstream from a luciferase reporter gene, and the basal and inducible activities of each were characterized by expression in Max cells, an immortalized pig cell line that responds to interferon and tumor necrosis factor alpha (TNF-alpha). All three classical class I but not nonclassical promoters responded to interferon. This was confirmed by the transactivation of SLA-1, but not SLA-7, after the co expression with interferon regulatory factors (IRFs), IRF-1, IRF-2, IRF-3, IRF-7, and IRF-9. Classical class I genes were activated by cotransfection with nuclear factor kappa B (NF-kappaB) p65 and by treatment of cells with TNF-alpha, although, unlike human promoter there was no synergistic effect with interferon. The greatest effect on classical class I promoters was coexpression with the class II transactivator (CIITA), important for constitutive transactivation. These results determine the differential regulation of porcine classical and nonclassical MHC class I and reflects their importance in antigen presentation during infection.

Uterine MHC Class I Molecules and β2-Microglobulin Are Regulated by Progesterone and Conceptus Interferons during Pig Pregnancy

“…Pig conceptus trophectoderm cells express high amounts of IFN-␥ mRNA from day 13 through day 20 of pregnancy, and immunoreactive IFN-␥ localizes to perinuclear membranes typically occupied by endoplasmic reticulum and Golgi apparatus as well as cytoplasmic vesicles within trophectoderm cells, suggesting trafficking and secretion of IFN-␥ into the uterine lumen (28,31). Interestingly, SLA-1, SLA-2, and SLA-3, but not SLA-6 or SLA-7, were reported to respond to both IFN-␥ and IFN-␣ in a pig kidney cell line (55). Although results of the present study are consistent with those of Tennant et al (55) for SLA-1, SLA-2, and SLA-3, there are differences between in vivo and in vitro results for SLA-6 and SLA-7.…”

“…Interestingly, SLA-1, SLA-2, and SLA-3, but not SLA-6 or SLA-7, were reported to respond to both IFN-␥ and IFN-␣ in a pig kidney cell line (55). Although results of the present study are consistent with those of Tennant et al (55) for SLA-1, SLA-2, and SLA-3, there are differences between in vivo and in vitro results for SLA-6 and SLA-7. It is perhaps not surprising that stromal cells in vivo, which have distinct spatial relationships to other cell types and the extracellular matrix, respond differently to IFNs than do isolated and cultured kidney cells.…”

Sequence-Based Genotyping of Expressed Swine Leukocyte Antigen Class I Alleles by Next-Generation Sequencing Reveal Novel Swine Leukocyte Antigen Class I Haplotypes and Alleles in Belgian, Danish, and Kenyan Fattening Pigs and Göttingen Minipigs

“…Of these, only the SLA-1, SLA-2 , and SLA-3 genes encode functional proteins with known relevance to CD8 T cell activation. Of the 3 SLA loci, the SLA-2 allele is transcribed at a higher level than SLA-1 , and SLA-3 is the allele with the lowest transcription level (6–8). Although thousands of SLA class I alleles are expected to exist, only 193 classical class I alleles have been identified and officially designated by the International Society for Animal Genetics (ISAG) and the International Union of Immunological Societies (IUIS) Veterinary Immunology Committee (VIC) SLA (ISAG/IUIS-VIC) Nomenclature Committee thus far, including 70 SLA-1, 87 SLA-2, and 36 SLA-3 alleles.…”

Transcription variants of SLA-7, a swine non classical MHC class I gene

“…It has been shown that SLA-Ib genes are expressed in a less restricted manner than the HLA-Ib genes [12,13] despite a predominant transcription in the lymphoid organs, the lung and the digestive tract [13]. In addition, conversely to the SLA-Ia genes, transfection experiments have revealed that the promoters of SLA-7 and SLA-6 do not respond to interferon, suggesting distinct regulatory systems for pig MHC class Ia and Ib genes, as in human [14]. Our aim was to focus on the transcription of the SLA-7 gene known to have a unique reference transcript [12].…”